Tetrahedron Letters No. 33, pp. 3131-3132, 1971. Pergamon Press. Printed in Great Britain.

STEREOCHEMISTRY OF EVONINE, NEO-EVONINE, EUONYMINE, AND NEO-EUONYMINE,

ALKALOIDS OBTAINED FROM EUONYMUS SIEBOLDIANA BLUME

Hiroshi Wada, Yoshikazu Shizuri, Kimio Sugiura, Kiyoyuki Yamada, and Yoshimasa Hirata

Chemical Institute, Faculty of Science, Nagoya University, Chikusa, Nagoya, Japan

(Received in Japan 5 July 1971; received in UK for publication 20 July 1yTl)

We have recently established the structures of four alkaloids, evonine l_, neo-evonine 2,

euonymine 2, and neo-euonymine 4_, obtained from Euonymus Sieboldiana Blume. 1

In this paper

the stereochemistry of these alkaloids is presented. The configurations of two asymmetric

centers in the evoninic acid moiety were already determined by Pailer and Libiseller. 2

Stereochemistry of evonine L and neo-evonine 2. The C-ring is necessarily attached to

the B-ring by two axial bonds at C-6 and C-10 of the B-ring on steric ground. Regarding the

A/B ring juncture two configurations (cis and trans) are possible, and it was proved by the --

intramolecular nuclear Overhauser effects (NOE) on pentadesacetylevonine acetonide diacetate

(prepared by acetylation of pentadesacetylevonine acetonidela with Ac20/pyridine) that the ring

juncture is trans: i) irradiation of the 11-methylene group (6 4.27) caused an increase (20%)

in the signal intensity of 5-H (6 6.35), and ii) an enhancement (8%) of the signal intensity of

5-H was detected on irradiation of 12-Me (6 1.67). These results of NOE indicate not only the

trans nature of the A/B ring juncture, but that these three groups (S-H, ll-CH2, and IZ-Me) are

axial in each chclohexane ring which is necessarily in a chair conformation. Since the acetyl

migration from Cl-OH to Cl1 -OH was observed during the Pb(OAc)4 oxidation of a derivative of A, lb

the C-11 methylene group and Cl-OH are in a cis arrangement. The coupling constant between

1-H and 2-H is in a range of 3.2 - 3.8 Hz on a variety of derivatives of 1, indicating that

these vicinal hydrogens are cis. - The cis relationship between 3-H and 12-Me was deduced from -

the observation of the NOE between 3-H and 12-Me: on irradiation of the 12-Me signal (6 1.67)

the intensity of the 3-H signal (6 4.79) was increased (~15%).

Formation of an acetonide (pentadesacetylevonine acetonide la) between Cl1 -OH and C8-OH revealed

that the 11-methylene group and C8-OH are cis. The NOE was observed between 8-H and 14-Me: -

when the 14-Me signal (6 1.57) was irradiated on neo-evonine methylether lc , an increase (30%) of

3131

3132 No.33

the 8-H signal intensity (6 4.91) occurred, demonstrating the configuration of 14-Me as shown in

1. The stereochemistry of evonine and neo-evonine is thus established as A and 2, respectively.

Stereochemistry of euonymine 3 and neo-euonymine 4. The LiAlH4 reduction of l_ afforded

two polyhydroxy compounds diastereoisomeric at C-7 (euonyminol la and iso-euonyminolla), one of

which (euonyminol) was shown to be identical with the sesquiterpene part of euonymine. lc

Since the coupling constant of 8-H was 6.0 Hz in euonyminol octaacetate la,lc and 10.0 Hz in

iso-euonyminol octaacetate, la,lc 7-H and 8-H are cis (equatorial-axial) for the former, and -

trans (axial-axial) for the latter. Further, the NOE was observed between S-H and 7-H in iso-

euonyminol octaacetate (13% increase). The stereochemistry of euonymine and neo-euonymine

was determined as 3 and 4. N h

Some aspects of the NMR spectra of evonine 1 and the derivatives. In the NMR spectra of

J and the derivatives, characteristic signals were observed, presumably owing to the complex and

rigid skeleton and

appeared at 6 6.72

and 6.04, J = 11.7

seems to be partly

the presence of many functional groups. A doublet (J -: 1.0 Hz) due to S-H

and the signal of 15-methylene group was observed as an AB quartet (6 3.76

Hz) separated by 2.3 ppm in 1: the presence of a pyridine ring in the molecule

responsible for the phenomena (CDC13,lOO MHz).

Acknowledgements. The authors are grateful to Dr. T. Nishida (Nippon Electric Varian, Ltd.)

and Mr. T. Kondo (Dept. of Agr. Chem., Nagoya Univ.) for NOE measurements (CDC13, 100 MHz).

1.a) H. b) Y. c) K.

2. M.

0

1: evonine R=Ac, X=0 N

2: neo-evonine R=H, X=0

2: euonymine R=/J,c, X=<iAc

4_: neo-euonymine R=H, X=<iAc

REFERENCES

Wada, Y. Shizuri, K. Yamada, and Y. Hirata, Tetrahedron Letters, in press. Shizuri, H. Wada, K. Sugiura, K. Yamada, and Y. Hirata, Tetrahedron Letters, in press. Sugiura, Y. Shizuri, H. Wada, K. Yamada, and Y. Hirata, Tetrahedron Letters, in press.

Pailer and R. Libiseller, Monatsh. Chem., 9& 511 (1962).